Human low density lipoprotein (LDL) may exist in either a monodisperse or a polydisperse state. Polydisperse LDL is most commonly found in association with hypertriglyceridemia and diabetes mellitus. Physical studies on polydisperse LDL reveal a family of discrete lipoproteins within the LDL class which differ in molecular size. Preliminary metabolic studies suggest that these lipoproteins are formed from VLDL by two separate pathways, and that these low density lipoproteins are catabolized in a sequential fashion in accord with their molecular size. The biological import of LDL polydispersity is indicated by the early mortality of severely affected patients. The objectives of this study are as follows: (1) To investigate the structural organization of polydisperse LDL, determining the relationships between lipid and apoprotein in different sized LDL. Also, to determine whether poly and monodisperse LDL arise as a consequence of differences in the primary structure of their apoproteins, in accord with clinical observations suggesting a familial association. (2) To puruse preliminary observations on the metabolic pathways for synthesis and catabolism of mono and polydisperse LDL, delineating those pathways which generate the polydisperse state. Previously developed kinetic techniques using 3H-leucine will be refined and coupled with computerized modeling of the data. (3) To explore the biological import of structural differences in LDL, utilizing tissue culture of human arterial endothelial and smooth muscle cells, asking whether structural differences cause altered cell growth characteristics, different LDL binding affinities to cellular receptors, differences in lipid transfer from LDL to cell, and differences in repression of cellular cholesterol synthesis.